The proto-oncogene, c-fms, has been described in both mature cat macrophages and undifferentiated and human tumors, and normal human bone marrow cells. The c-fms proto-oncogene is expressed during human monocyte differentiation and the c-fms product has been related to the receptor for mononuclear phagocyte growth factor (CSF-1). The purpose of this investigation is: (1) to screen for the presence of the c-fms proto-oncogene in the in vivo serially transplanted F344/N mononuclear leukemic cell lines and, (2) to initiate studies on the isolation and expression of the gene product. This will provide insight on the origin of the tumor and aid in providing diagnostic criteria for the tumor. In addition, this tumor line may provide a valuable source of genetic material for investigations into the molecular biology of the c-fms protooncogene and its potential effect on MNCL expression. Our investigation indicates the presence of c-fms oncogene isolated from both spontaneously occurring MNCL tumors and these leukemic cells appear to have a normal karyotype (except for an unusual subterminal x- chromosome variant) and possess hematopoietic differentiation antigens of both monocytes and lymphocytes, in vivo transplanted MNCL tumor lines. In situ hybridization technique using monolayer of heterogeneous leukemic cell population are being pursued to allow identification of c-fms in specific cell types.